title: Antiproliferative effects of palladium(II) complexes of 5-nitrosopyrimidines and interactions with the proteolytic regulatory enzymes of the renin-angiotensin system in tumoral brain cells.
abstract: Seventeen new palladium(II) complexes of general formulaes PdCl2L, PdCl(LH-1)(solvent) and PdCl2(PPh3)2L containing pyrimidine ligands derived from 6-amino-5-nitrosouracil and violuric acid have been prepared and characterized by elemental analysis, IR and NMR ((1)H and (13)C) methods and, two of them, PdCl(DANUH-1)(CH3CN)]·½H2O and [PdCl(2MeOANUH-1)(CH3CN)] by X-ray single-crystal diffraction (DANU: 6-amino-1,3-dimethyl-5-nitrosouracil; 2MeOANU: 6-amino-2-methoxy-5-nitroso-3H-pyrimidin-4-one). The coordination environment around palladium is nearly square planar in the two compounds with different supramolecular arrangements. Crystallographic and spectral data are consistent with a bidentate coordination mode through N5 and O4 atoms when the ligands act in neutral form and N5 and N6 atoms in the monodeprotonated ones. The cytotoxicity of the complexes against human neuroblastoma (NB69) and human glioma (U373-MG) cell lines has been tested showing a considerable antiproliferative activity. Also, the study of the effects of palladium(II) complexes on the renin-angiotensin system (RAS) regulating proteolytic regulatory enzymes aminopeptidase A (APA), aminopeptidase N (APN) and insulin-regulated aminopeptidase (IRAP) shows a strong dependence on the compound tested and the tumoral cell type, also affecting different catalytic routes; the compounds affect in a different way the activities of enzymes of the RAS system, changing their functional roles as initiators of cell proliferation in tumors as autocrine/paracrine mediators.
authors.affiliation: Departamento de Química Inorgánica y Orgánica, Universidad de Jaén, 23071 Jaén, Spain.
authors.forename: Nuria A
authors.initials: NA
authors.lastname: Illán-Cabeza
authors.forename: Antonio R
authors.initials: AR
authors.lastname: García-García
authors.forename: José M
authors.initials: JM
authors.lastname: Martínez-Martos
authors.forename: María J
authors.initials: MJ
authors.lastname: Ramírez-Expósito
authors.forename: Miguel N
authors.initials: MN
authors.lastname: Moreno-Carretero
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D018826:CD13 Antigens / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D010122:Cystinyl Aminopeptidase / Q000378:metabolism; D043384:Glutamyl Aminopeptidase / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009603:Nitroso Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D009928:Organ Specificity; D010165:Palladium / Q000737:chemistry*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D009603:Nitroso Compounds; D014498:Uracil; D010165:Palladium; D018826:CD13 Antigens; D010122:Cystinyl Aminopeptidase; C105964:leucyl-cystinyl aminopeptidase; D043384:Glutamyl Aminopeptidase; C008756:palladium chloride
keywords: Antiproliferative effect; Crystal structure; Palladium(II) complexes; Renin–angiotensin system; Uracil; Violuric acid